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Introduction: Nucleoporin 98 (NUP98) fusion proteins are recurrently found in leukemia and are associated with unfavorable clinical outcomes. They are distributed to the nucleus and contribute to leukemogenesis via aberrant transcriptional regulation. We previously identified NUP98‐BPTF (NB) fusion in patients with T‐cell acute lymphoblastic leukemia (T‐ALL) using next‐generation sequencing. The FG‐repeat of NUP98 and the PHD finger and bromodomain of bromodomain PHD finger transcription factor (BPTF) are retained in the fusion. Like other NUP98 fusion proteins, NB is considered to regulate genes that are essential for leukemogenesis. However, its target genes or pathways remain unknown. Materials and Methods: To investigate the potential oncogenic properties of the NB fusion protein, we lentivirally transduced a doxycycline‐inducible NB expression vector into mouse NIH3T3 fibroblasts and human Jurkat T‐ALL cells. Results: NB promoted the transformation of mouse NIH3T3 fibroblasts by upregulating the proto‐oncogene Pim1, which encodes a serine/threonine kinase. NB transcriptionally regulated Pim1 expression by binding to its promoter and activated MYC and mTORC1 signaling. PIM1 knockdown or pharmacological inhibition of mTORC1 signaling suppressed NB‐induced NIH3T3 cell transformation. Furthermore, NB enhanced the survival of human Jurkat T‐ALL cells by inactivating the pro‐apoptotic protein BCL2‐associated agonist of cell death (BAD). Conclusion: We demonstrated the pivotal role of NB in cell transformation and survival and identified PIM1as a key downstream target of NB. These findings propose a promising therapeutic strategy for patients with NB fusion‐positive leukemia. [ABSTRACT FROM AUTHOR]

The present study used haptic technology to determine the safe forceps grip force for preventing organ damage when handling the intestinal tract. The small intestines of ten male beagle dogs (weighing 9.5–10 kg) were grasped with the entire forceps for one minute; the small intestines were then pulled out of the forceps and evaluated for damage. The force at which the shaft inside the forceps was pulled to close the tip of the forceps was defined as the grip force. Small intestine damage was classified into macroscopic (serosal defects, hemorrhage, hematomas, grip marks) and microscopic (damage layer to the mucosa, submucosa/muscularis mucosa, inner orbicularis muscle, external longitudinal muscle, serosa/subserosa). Grip marks and damage layer to the serosa/subserosa have been considered as acceptable safety margins when grasping the small intestines of beagle dogs. The macroscopic findings showed that the maximum grip force that produced a 0% incidence of hemorrhage and hematoma was 15 N. At the microscopic level, the maximum grip force that produced a 0% incidence of external longitudinal muscle injury was 15 N, respectively. A grip force of 15 N does not damage the small intestines of beagle dogs. [ABSTRACT FROM AUTHOR]

Tumor‐associated macrophages (TAMs) are associated with a poor prognosis of diffuse large B‐cell lymphoma (DLBCL). As macrophages are heterogeneous, the immune polarization and their pathological role warrant further study. We characterized the microenvironment of DLBCL by immunohistochemistry in a training set of 132 cases, which included 10 Epstein–Barr virus‐encoded small RNA (EBER)‐positive and five high‐grade B‐cell lymphomas, with gene expression profiling in a representative subset of 37 cases. Diffuse large B‐cell lymphoma had a differential infiltration of TAMs. The high infiltration of CD68 (pan‐macrophages), CD16 (M1‐like), CD163, pentraxin 3 (PTX3), and interleukin (IL)‐10‐positive macrophages (M2c‐like) and low infiltration of FOXP3‐positive regulatory T lymphocytes (Tregs) correlated with poor survival. Activated B cell‐like DLBCL was associated with high CD16, CD163, PTX3, and IL‐10, and EBER‐positive DLBCL with high CD163 and PTX3. Programmed cell death‐ligand 1 positively correlated with CD16, CD163, IL‐10, and RGS1. In a multivariate analysis of overall survival, PTX3 and International Prognostic Index were identified as the most relevant variables. The gene expression analysis showed upregulation of genes involved in innate and adaptive immune responses and macrophage and Toll‐like receptor pathways in high PTX3 cases. The prognostic relevance of PTX3 was confirmed in a validation set of 159 cases. Finally, in a series from Europe and North America (GSE10846, R‐CHOP‐like treatment, n = 233) high gene expression of PTX3 correlated with poor survival, and moderately with CSF1R, CD16, MITF, CD163, MYC, and RGS1. Therefore, the high infiltration of M2c‐like immune regulatory macrophages and low infiltration of FOXP3‐positive Tregs is associated with a poor prognosis in DLBCL, for which PTX3 is a new prognostic biomarker. [ABSTRACT FROM AUTHOR]

Diffuse large B‐cell lymphoma with MYC rearrangement is defined as double/triple‐hit lymphoma (DHL/THL) or single‐hit lymphoma (SHL) by the inclusion of the BCL2 and BCL6 rearrangements status. DHL/THL is called as "high‐grade B‐cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements" in the World Health Organization 2017 Classification of Tumors of Hematopoietic and Lymphoid Tissues. To find a prognostic biomarker of DHL/THL, we firstly examined 19 cases (molecular analysis series;10 cases of DHL/THL and 9 cases of SHL) with gene expression profile analysis. The gene expression profile analysis showed that the high expression of AICDA was associated with an adverse prognosis in DHL/THL, but not in SHL. Then, we evaluated immunohistochemical expression of AID, the protein product of AICDA, in 50 cases (molecular analysis series of 19 cases and additional immunohistochemistry series of 31 cases; 12 cases of DHL/THL and 19 cases of SHL) and confirmed that its expression was also associated with an adverse prognosis in DHL/THL. Therefore, AICDA and AID can be a predictor of an adverse clinical outcome in DHL/THL and immunohistochemistry of AID is useful to find DHL/THL‐adverse prognosis group. [ABSTRACT FROM AUTHOR]

The incidence of synchronous multiple primary lung cancers has increased in recent years, however, there are few reports of cases involving small cell carcinoma. A 72-year-old man was referred to our department because of an abnormal shadow on chest radiography. He was receiving treatment for pulmonary fibrosis, emphysema, rheumatoid arthritis, and prostate cancer. Computed tomography revealed two lung nodules in the left lower lobe. A definitive diagnosis was unable to be made based on transbronchial lung biopsy. Positron emission tomography demonstrated abnormal fluorodeoxyglucose uptake in the two lung nodules and lung cancer (cT3N0M0) was suspected. Thoracoscopic partial resection of the left lower lobe was performed. As primary lung cancer was diagnosed using the frozen specimen, we performed left lower lobectomy with lymph node dissection. Pathological examination of the S9 and S6 tumors revealed combined small cell carcinoma and squamous cell carcinoma, respectively. Both tumors were separated and diagnosed as synchronous multiple primary lung cancers. No lymph node metastasis was found. We report a rare case of synchronous multiple primary lung cancers, including small cell carcinoma.

A 68-year-old man who underwent cholecystectomy for acute cholecystitis and was diagnosed with gallbladder duct carcinoma was referred to our hospital. Postoperative computed tomography showed thickening of the middle to lower bile duct without any tumorous lesions. Endoscopic retrograde cholangiopancreatography and intraductal ultrasonography revealed irregular wall thickening of the lower bile duct and apparent infiltration of gallbladder duct tumor to the common bile duct without pancreaticobiliary maljunction. Subtotal stomach-preserving pancreaticoduodenectomy was performed. Pathological examination showed papillary adenocarcinoma and tubular adenocarcinoma in the gallbladder duct and BilIN-3 lesion in the distal bile duct. The final diagnosis was biliary simultaneous multicentric cancer without pancreaticobiliary maljunction.

A 29-year-old female with ulcerative colitis was found to have advanced sigmoid colon cancer on colonoscopy. Computed tomography (CT) was performed after colonoscopy for the evaluation of metastasis. CT colonography (CTC) could be understood adding carbon dioxide because of soon after colonoscopic examination. Images of CTC were evaluated by two- and three-dimensional images including virtual endoscopic, virtual colon dissection and air images, and then compared with conventional endoscopic images. Virtual endoscopic images of flat elevated cancer with shallow ulcer were similar to those findings by conventional endoscopy. This lesion could be depicted by computer-aided detection.